New Therapeutic Approaches Using Hydrogen Sulfide Donors in Inflammation and Immune Response.

Significance: Inflammation and immune response are associated with many pathological disorders, including rheumatoid arthritis, lupus, heart failure, and cancer(s). In recent times, important roles of hydrogen sulfide (H2S) have been evidenced by researchers in inflammatory responses, as well as immunomodulatory effects in several disease models. Recent Advances: Numerous biological targets, including cytochrome c oxidase, various kinases, enzymes involved in epigenetic changes, transcription factors, namely nuclear factor kappa B and nuclear factor erythroid 2-related factor 2, and several membrane ion channels, are shown to be sensitive to H2S and have been widely investigated in various preclinical models. Critical Issues: A complete understanding of the effects of H2S in inflammatory and immune response is vital in the development of novel H2S generating therapeutics. In this review, the biological effects and pharmacological properties of H2S in inflammation and immune response are addressed. The review also covers some of the novel H2S releasing prodrugs developed in recent years as tools to study this fascinating molecule. Future Directions: H2S plays important roles in inflammation and immunity-related processes. Future researches are needed to further assess the immunomodulatory effects of H2S and to assist in the design of more efficient H2S carrier systems, or drug formulations, for the management of immune-related conditions in humans. Antioxid. Redox Signal. 35, 341-356.